E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Women with locally advanced/recurrent breast cancer |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Phase I Objective: To confirm safety reported in Japanese studies. Endpoint: Patient reported maximum intra-tumoural pain intensity over duration of treatment.
Phase II Objective: To test efficacy. Endpoint: Tumour response 3 months post-radiotherapy according to RECIST 1.1 criteria.
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E.2.2 | Secondary objectives of the trial |
Phase I Objective: To further characterise safety and to record efficacy. Endpoints: •Proportion of patients with severe pain at any time before and up to 24 hours after any of the KORTUC injections. Server pain is defined as scoring a max grade ≥5 above baseline •Duration of pain score ≥1 higher than baseline at each time point •Proportion of patients needing additional pain medication •Frequency and completeness of returned questionnaires. •Proportion of patients with grade ≥3 acute skin toxicity at any time from start of radiotherapy to 4 weeks after completion •Worst grade of skin acute toxicity from start of radiotherapy to 4 weeks post-radiotherapy •Adherence to acute toxicity assessments •Proportion of patients with any grade radiation dermatitis •Incidence of tumour lysis syndrome •Tumour response 3 months post-radiotherapy according to RECIST 1.1 criteria
Phase II Objective: To further characterise efficacy and safety. Endpoints: •Proportion of patients with severe pa |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Primary locally advanced breast cancer, or locally recurrent breast cancer with/without metastases •Radical/high dose palliative radiotherapy required for lifetime control of local morbidities •Patient physically and mentally fit for radical/high dose palliative radiotherapy •Target tumour accessible for intra-tumoural injection •At least one tumour diameter ≥40 mm measurable by ultrasound or magnetic resonance imaging •Patient available for minimum 3 months follow up post-treatment prior to any surgical resection •Negative pregnancy test within 7 days of starting radiotherapy in women of child bearing potential and an ability/willingness to protect against pregnancy for 3 months post-radiotherapy •Patient offers written informed consent |
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E.4 | Principal exclusion criteria |
• Prior radiotherapy to the target area • Anatomical location &/or extent of disease difficult to access for safe intra-tumoural drug injections, for example by virtue of contiguous major blood vessels and/or brachial plexus |
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E.5 End points |
E.5.1 | Primary end point(s) |
Phase I Objective: To confirm safety reported in Japanese studies. Endpoint: Patient reported maximum intra-tumoural pain intensity over duration of treatment.
Phase II Objective: To test efficacy. Endpoint: Tumour response 3 months post-radiotherapy according to RECIST 1.1 criteria.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Phase I Pain at target tumour site: 0-24 hours after each injection of drug.
Phase II Complete tumour response: 3 months post-radiotherapy (US/MRI). |
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E.5.2 | Secondary end point(s) |
Phase I Endpoints: •Proportion of patients with severe pain at any time before and up to 24 hours after any of the KORTUC injections. Server pain is defined as scoring a max grade ≥5 above baseline •Duration of pain score ≥1 higher than baseline at each time point •Proportion of patients needing additional pain medication •Frequency and completeness of returned questionnaires. •Proportion of patients with grade ≥3 acute skin toxicity at any time from start of radiotherapy to 4 weeks after completion •Worst grade of skin acute toxicity from start of radiotherapy to 4 weeks post-radiotherapy •Adherence to acute toxicity assessments •Proportion of patients with any grade radiation dermatitis •Incidence of tumour lysis syndrome •Tumour response 3 months post-radiotherapy in accordance with RECIST criteria 1.1
Phase II Endpoints: •Proportion of patients with severe pain at any time before and up to 24 hours after any of the KORTUC injections. Server pain is defined as scoring a max grade ≥5 above baseline •Frequency and duration of pain score ≥1 at each time point •Proportion of patients needing additional pain medication •Frequency and completeness of returned questionnaires Worst grade of skin acute toxicity from start of radiotherapy to 4 weeks post-radiotherapy •Proportion of patients with any grade radiation dermatitis •Incidence of Tumour lysis syndrome •Planned/unplanned tumour excision & pathological response •Local progression-free survival at 24 months
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Phase I Tumour response 3 months post-radiotherapy. All other endpoints in Phase I: start of radiotherapy until skin reactions resolve to CTCAE v4.02 grade 0-1 (min 4 weeks after end of radiotherapy).
Phase II Incidence of tumour lysis syndrome: second & third weeks of radiotherapy. Planned/unplanned tumour excision & pathological response: more than 3 months post-radiotherapy. All other endpoints in Phase II: 0-24 hours after each injection of drug weekly during/after radiotherapy until CTCAE 0-1 (min 4 weeks post-radiotherapy). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Phase I "run in" study to confirm findings by collaborators in Japan in 12 UK patients. |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Radiotherapy without drug |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 1 |